This was the fifth year of the Section on Affective Neuroscience and Pain, and the lab continued to grow and see former fellows move on to exciting new positions. One postdoctoral fellow (IL) began an Assistant Professor position, another received a competitive AAAS fellowship and will be working as a program officer with NIMH, and three new fellows (one postdoc, two postbacs) joined the lab in 2019. We continued to make strong progress on our human subjects protocol Neural and psychological mechanisms of pain perception. The protocol includes five sub-studies designed to a) isolate different aspects of pain modulation, b) compare acute pain modalities (e.g., thermal pain versus shock-induced pain), and c) compare and contrast pain with other hedonic and perceptual domains (e.g., taste). In all studies, we measure decisions about pain experience (self-report) as well as neural and physiological responses to noxious stimuli that cause pain. During analysis, we combine computational modeling with advanced neuroimaging analyses to isolate the neural and psychological mechanisms that mediate the effects of expectations, attention, and emotion on subjective pain. Our protocol requires all participants to go through an initial calibration session, following screening. Participants complete questionnaires, and then undergo a procedure that measures pain ratings in response to noxious heat stimuli and determines each participants pain threshold and tolerance. 279 individuals have completed this procedure to date (48 participants so far during Year 5 of the protocol, FY18-19). We published one manuscript from this protocol in the past fiscal year (Mischkowski et al., Pain, 2019). We analyzed the relationship between temperature, pain, and autonomic responses (skin conductance and pupil dilation), and found that autonomic responses to objective stimuli depend on whether a response is classified as painful or not, and likewise the intensity of the pain drives the bodys response, rather than the objective stimulus temperature. This paper has been well-received with a commentary written in response (Zaman et al., 2019) and was selected as an Editors pick at the journal. We have one manuscript under revision and are preparing additional manuscripts from a set of studies in which data collection was completed on this protocol in FY17. We examined the effects of classical conditioning and instructed knowledge on pain and reversal learning. We combined fMRI subjects data with data from 23 participants who completed the task outside the scanner and measured the influence of anxiety on pain. We found that individuals who reported high anxiety showed stronger reversals of pain in response to instruction, yet showed reduced reversals in autonomic responses (Atlas et al., Invited revision, Journal of Abnormal Psychiatry). Both pain and arousal were related to individual differences in state anxiety within our healthy volunteers. We are currently following up on these findings through a collaboration with Dr. Daniel Pine (NIMH) to test reversal learning and pain in clinically anxious individuals. In addition, we have completed fMRI analyses from 40 healthy volunteers who completed the task in the fMRI scanner. We plan to submit 1-2 manuscripts on this work in the coming year which examine how instructions and learning shape subjective pain (Atlas et al., In prep), and discuss different approaches to noise reduction using multi-echo fMRI scanning (Yu et al., In progress). We also analyzed data from our second fMRI sub-study, which tests whether cue-based expectancies and treatment-based expectancies (i.e. placebo responses) modulate pain through dissociable pathways (Necka et al., In prep). This study crosses conditioned cues with a placebo analgesia manipulation. 40 subjects completed the task in the fMRI scanner. We found that cue-based pain modulation was reduced under placebo, indicating that placebo and cue-based modulation interact to shape subjective pain. We are currently completing fMRI analyses and anticipate submitting a manuscript for publication in FY20. We are currently completing fMRI data collection from a third sub-study that measures the relationship between pain and pleasant and unpleasant taste perception and how expectations modulate perception across domains (Lee et al., In progress). We worked with the Section on Instrumentation to build an fMRI-compatible gustometer (taste-delivery device) that can deliver juices in the fMRI scanner and completed a pilot sub-study in FY18, which allowed us to perform power analyses for the fMRI study. This study measures how predictive cues modulate pain, sugar perception, and salt perception. This study involves two visits: one outside the scanner to identify each subjects threshold and tolerance, and one inside the scanner in which participants are randomized to receive sugar, salt, or heat in a conditioning paradigm. We are now well underway with the fMRI version of the study: 45 participants have completed all visits, and 10 additional participants have completed the first visit to select temperatures and tastants prior to the fMRI study. Data collection will be complete when 60 participants complete the fMRI session (20 per group). The overall goal of this project is to isolate domain-specific as well as domain-general mechanisms that underlie expectancy, affective learning, and perception. This project was led by our newest postdoc, In-Seon Lee, and is supported by two postbacs and our data analyst, as Dr. Lee is beginning a faculty position in Korea starting in September. We anticipate that the manuscript for this study will be submitted in FY20. Finally, we also published or submitted several collaborative papers, reviews, and commentaries that are relevant to this line of research including one paper on brain-body relationships and pain specificity (Lee et al., under revision), one paper on dynamic connectivity and pain perception (Necka et al., 2019), two papers on instructed learning (Atlas 2019; Atlas et al., 2019, PsyRxiv), one paper on pain neuroimaging (Moayedi, Salomons, and Atlas 2019), and one collaborative papers on placebo analgesia (Zunhammer et al., 2019).